Other highlights in the January 19 JNCI

01/13/05

Adding Multiple HPV Types to DNA Tests May Lead to Unnecessary Exams

Adding more types of human papillomavirus to the current HPV DNA test would detect relatively few additional cases of cervical cancer but would result in thousands of additional women without cancer receiving unnecessary cervical exams, according to a new study.

The use of HPV testing in the detection and prevention of cervical cancer is increasing. The U.S. Food and Drug Administration has approved an HPV DNA test that targets 13 HPV types as an adjunct to Pap screening in women age 30 and older. However, most HPV infections are benign. It has been suggested that the HPV DNA test could be improved with the addition of more HPV types, but it is not known what effect this would have on the test's accuracy.

To evaluate the impact of modifying the HPV DNA test, Mark Schiffman, M.D., M.P.H., of the National Cancer Institute, and colleagues analyzed data from two large NCI studies. They found that testing for more than 10 HPV types increased the proportion of false-positive results by far more than it increased the proportion of true-positive results. The authors conclude that the minimal increases in detection gained from adding HPV types to the existing DNA test must be weighed against the projected burden to thousands of women falsely labeled as being at high risk of cervical cancer.

The nearly sixfold increase in one of the two most common forms of esophageal cancer over the last 25 years is not the result of overdiagnosis or reclassification and represents a real rise, according to a new study.

About 14,250 people in the United States were diagnosed with esophageal cancer in 2004, and half of those cases were adenocarcinoma. Although esophageal adenocarcinoma is rare, its incidence has increased by sixfold over the last 25 years. However, the source of the increase has not been determined. It is possible that either overdiagnosis--the detection of disease that would not have produced signs or symptoms before death--or reclassification--a change in how diagnostic terminology is applied--could explain the rise.

Heiko Pohl, M.D., and H. Gilbert Welch, M.D., M.P.H., of the Department of Veterans Affairs Medical Center in White River Junction, Vt., analyzed data from the Surveillance, Epidemiology, and End Results (SEER) database to determine if overdiagnosis or reclassification could explain the increase in esophageal adenocarcinoma. However, they found no evidence that either source could explain the increase and conclude that the rise in esophageal adenocarcinoma must be real.

The human protein cripto-1 (CR-1) promotes cell transformation and increases migration and invasion in various epithelial cell lines. A new study has found that CR-1 also plays an important role in angiogenesis.

David S. Salomon, Ph.D., of the National Cancer Institute, and colleagues investigated whether CR-1 stimulates angiogenesis by using human umbilical vein endothelial cells and CR-1-transfected human breast cancer cells. They found that the addition of CR-1 to the human umbilical vein endothelial cells stimulated their proliferation, migration, and invasion and induced their differentiation into vascular-like structures. In addition, tumors formed by the CR-1-transfected breast cancer cells had a higher density of microvessels than tumors formed by cells without CR-1. The authors conclude that CR-1 appears to have an important role in angiogenesis.

Epigenetic changes, such as DNA methylation and histone acetylation, can have profound effects on the development and progression of cancer. Rajvir Dahiya, Ph.D., of the University of California San Francisco, and colleagues review the current literature on these two epigenetic changes and their role in prostate cancer. They discuss interactions between the two classes of changes and how they may be exploited to identify potential tumor biomarkers for early diagnosis and risk assessment of prostate cancer and to design potential therapeutic strategies.

The Selenium and Vitamin E Cancer Prevention Trial (SELECT), which began in 2001, is a phase III randomized, placebo-controlled trial of selenium and vitamin E for the prevention of prostate cancer. The participants--32,400 men from the United States, Puerto Rico, and Canada--will receive supplements of selenium, vitamin E, or both for 7 to 12 years. They will be encouraged to receive annual prostate cancer screenings but will be allowed to follow community screening standards and personal preferences. In a commentary, Scott M. Lippman, M.D., of the University of Texas M. D. Anderson Cancer Center in Houston, and colleagues discuss the design problems encountered in the development of SELECT, including measures to ensure strong participation of African American men, who have the highest risk of prostate cancer in the world.